Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program

Laufey Geirsdottir, Eyal David, Hadas Keren-Shaul, Assaf Weiner, Stefan Cornelius Bohlen, Jana Neuber, Adam Balic, Amir Giladi, Fadi Sheban, Charles-Antoine Dutertre, Christine Pfeifle, Francesca Peri, Antonella Raffo-Romero, Jacopo Vizioli, Kaspar Matiasek, Christian Scheiwe, Stephan Meckel, Kerstin Mätz-Rensing, Franziska van der Meer, Finnbogi Rutur ThormodssonChristine Stadelmann, Noga Zilkha, Tali Kimchi, Florent Ginhoux, Igor Ulitsky, Daniel Erny, Ido Amit, Marco Prinz

Research output: Contribution to journalArticlepeer-review

Abstract

Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.

Original languageEnglish
Pages (from-to)1609-1622.e16
JournalCell
Volume179
Issue number7
DOIs
Publication statusPublished - 12 Dec 2019

Keywords

  • immunology
  • microglia
  • single-cell RNA-seq
  • systems biology
  • neurodegeneration

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